Experiments in the current project contribute to an understanding of how precise connections develop between neurons and their targets. Experimental and descriptive studies of a simple vertebrate system, the motor innervation of the chick embryo hindlimb, have shown that selective pathfinding by the growing tips of individual neurites (the "growth cones") plays a large role in the genesis of precise and orderly connections. The growth cones use navigational cues of two classes during their outgrowth. The first of these are highly specific cues that growth cone use to select the correct pathways at points where pathways diverge. The second set of cues delineate the pathways themselves. Experiments in this project are designed to characterize the spatial extent, source, and development of these axonal guidance cues, using nerve tracing techniques, simple ablation surgeries, and transplants between quail and chick embryos in which the donor tissues can be identified histologically. An important part of the projected study is to analyze the applicability of chimaeric operations between chick and quail to studies is to analyze the aplicability of chimaeric operations between chick and quail to studies of the nervous system. Preliminary results suggest that the chimaeric technique will be invaluable in studying the relationship between tissues in the embryonic environment and the navigation of growth cones. The specific objectives for the next year are to: (1) conclude experiments to determine if the quail/chick chimaeric surgical technique can be used in this system to study growth cone interactions with their environment. (2) conclude the mapping of quail motoneuron pools to determine what differences in axonal projection patterns in quail must be taken into account in analyzing chimaeras. (3) conclude experiments that assess whether navigational cues are provided by tissues between the spinal cord and the limb base. (4) begin embryonic surgeries designed to characterize the distal extent of specific cues that allow axons to choose between dorsal and ventral pathways at the limb base. Analysis of the navigational cues that are effective in specific neuronal pathfinding in the chick hindlimb system should give insights into the normal and abnormal development of the human nervous system.